DESCRIPTION: The inverse gradient in Coronary Heart Disease (CHD) by socioeconomic status is one of the major unsolved puzzles in epidemiology. Whitehall II is a longitudinal cohort study of 10,308 female and male British Civil Servants set up in 1985 to test the hypothesis that psychosocial factors and differences in nutrition might explain this inverse gradient. NHLBI has been instrumental in supporting the measurement of psychosocial characteristics, in particular the psychosocial work environment and social support. There have now been four phases of data collection in the study, of which two have involved clinical screening with measurement of blood pressure, ECG and a blood sample. Five year incidence data, based on self-report coronary endpoints suggest that standard coronary risk factors explain no more than a third of the gradient, but factors in the psychosocial environment and height appear to explain the major part of the social gradient in CHD. There are also clear social gradients in plasma fibrinogen and in markers of the metabolic syndrome suggestive of insulin resistance. It is not yet clear whether these biochemical factors may mediate the link between psychosocial factors and CHD. In the next phase of data collection (1997), mostly funded by core British support, the investigators plan a further clinical examination combined with assessment of neurohumoral (hypothalamic-pituitary-adrenal axis and adrenal medullary) functioning as markers of physiological pathways linking the psychosocial environment and CHD. In the next three years the investigators seek funding from NHLBI to analyze the association between biochemical factors and validated coronary endpoints, to examine whether biomedical factors mediate the relationship between the psychosocial environment and coronary heart disease. To do this they need to continue to collect information on sickness absence from the Civil Service, mortality from National Health Service Central Records, records of illness from family physicians and hospitals. They also request funding to validate our self-report measures of work characteristics and to measure 24 hour urinary catecholamines as a component of assessment of adrenal medullarv function to support measures of heart rate variability.